Role of P53 Status on Sensitivity to Thymidylate Synthase Inhibitors and Induction of Apoptosis

Thymidylate synthase (TS) catalyzes the methylation of dUMP to dTMP using 5,10-methylene-tetrahydrofolate (5,10-CH2-THF) (1). The expression of TS protein is regulated by its RNA binding capacity repressing the translation of its own mRNA and of p53 (2). TS expression is also inhibited by the tumor suppressor p53 (3).